Cited by 495Bacterial Cancer TherapyNanoparticle-Based Drug DeliveryGut microbiota and health

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Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy

Zheng, Di-Wei, Dong, Xue, Pan, Pei, Chen, Ke-Wei, Fan, Jin-Xuan, Cheng, Si-Xue, Zhang, Xian-Zheng·2019·Nature Biomedical Engineering

DOI 10.1038/s41551-019-0423-2

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Abstract

The microbiota in the human gut is strongly correlated with the progression of colorectal cancer (CRC) and with therapeutic responses to CRC. Here, by leveraging the higher concentration of the pro-tumoural Fusobacterium nucleatum and the absence of antineoplastic butyrate-producing bacteria in the faecal microbiota of patients with CRC, we show that-in mice with orthotopic colorectal tumours or with spontaneously formed colorectal tumours-oral or intravenous administration of irinotecan-loaded dextran nanoparticles covalently linked to azide-modified phages that inhibit the growth of F. nucleatum significantly augments the efficiency of first-line chemotherapy treatments of CRC. We also show that oral administration of the phage-guided irinotecan-loaded nanoparticles in piglets led to negligible changes in haemocyte counts, immunoglobulin and histamine levels, and liver and renal functions. Phage-guided nanotechnology for the modulation of the gut microbiota might inspire new approaches for the treatment of CRC.

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Authors: Zheng, D.-W., Dong, X., Pan, P., Chen, K.-W., Fan, J.-X., Cheng, S.-X., & Zhang, X.-Z.
Affiliations: Wuhan University (CN)
Corresponding author: Zhang, Xian-Zheng
ORCID: Dong, Xue
Pan, Pei
Chen, Ke-Wei
Fan, Jin-Xuan
Cheng, Si-Xue
Zhang, Xian-Zheng
Venue: Nature Biomedical Engineering
Publisher: Springer Science and Business Media LLC
Published: 2019-07-22
Volume: 3
Issue: 9
Pages: 717-728
ISSN: 2157-846X (ISSN-L)
DOI: 10.1038/s41551-019-0423-2
OpenAlex: W2963121075
Semantic Scholar: 94cc03369015ffa0b01be1420acac9b81fce02ac
Cited by: 495
References: 37
Citations by year: 2026: 77 · 2025: 92 · 2024: 96 · 2023: 87 · 2022: 53 · 2021: 45 · 2020: 39 · 2019: 5
FWCI: 18.93
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Biomedical Engineering (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords: colorectal cancer, gut microbiota, phage therapy, Fusobacterium nucleatum, irinotecan, dextran nanoparticles, chemotherapy response, butyrate-producing bacteria, orthotopic tumor model, piglet model
MeSH terms: Gastrointestinal Microbiome, Irinotecan, Animals, Antineoplastic Agents, Bacteria, Bacteriophages, Butyrates, Colonic Neoplasms, Dextrans, Disease Models, Animal, Drug Therapy, Immunoglobulins, Male, Mice, Inbred C57BL, Colorectal Neoplasms, Fusobacterium nucleatum, Cell Line, Tumor, Cell Proliferation, Mice, Nanoparticles

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Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy

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